Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pyrenes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,495 records · Page 83Linked to original sources
PubMedDate not supplied

Increased aryl hydrocarbon hydroxylase and prolyl hydroxylase activities in lung organ cultures exposed to benzo[a]pyrene.

Exposure of neo-natal rat lungs in organ culture to 10--25 microM benzo[a]pyrene (BaP) elevated the activities of aryl hydrocarbon hydroxylase (AHH) and prolyl hydroxylase (PH). Pyrene, a non-carcinogenic hydrocarbon did not elicit this response. Prolyl hydroxylase is an indicator of collagen synthesis and increased PH activity in the lungs reflects increased collagen synthesis. Our studies suggest that the earliest events in BaP-induced lung injury may include altered collagen metabolism.

Animals↗
PubMed1985

Quantitating exposure to chemical carcinogens: in vivo alkylation of hemoglobin by benzo[a]pyrene.

Mild acid hydrolysis of globin preparations from erythrocytes of mice, previously exposed topically to benzo[a]pyrene (BaP), releases tetrols which are detectable by HPLC/fluorescence analysis. If the mouse is exposed to radiolabelled BaP, radioactivity can be found in the acid-releasable tetrols. Treatment of the globin preparations prior to acid hydrolysis with proteolytic enzymes, but not enzymes that degrade nucleic acids, followed by dialysis, reduces the amount of tetrols that can be detected. Because the procedure used for the isolation of globin preparations from mouse blood precludes the presence of non-covalently bound BaP or its cellular metabolites, it is concluded that prior to acid hydrolysis, the tetrols were covalently attached to the hemoglobin, most probably as a result of the metabolic conversion of the applied carcinogen to the chemically reactive anti-diol epoxide. There is a dose response relationship between the amount of BaP applied to the skin of the mouse and the occurrence, 24 h later, of BaP adducts to hemoglobin, while the adduct, once formed, disappears with a half-life of 6 days. The amount of anti-benzo[a]pyrene diol epoxide (anti-BaPDE) binding to DNA and hemoglobin at various doses of BaP appears to be qualitatively similar.

Alkylating Agents↗
PubMed1988

In vivo metabolism of nasally instilled benzo[a]pyrene in dogs and monkeys.

Metabolism of inhaled materials deposited in the nasal cavity potentially influences their biological fate and toxicity. Metabolic enzymes, including cytochrome P-450-dependent monooxygenases, are not evenly distributed throughout the nasal cavity. The purpose of this study was to determine whether benzo[a]pyrene (BaP) deposited in the nasal cavity could be metabolized and cleared by the nasal tissue in the ethmoid and maxillary turbinate regions of Beagle dogs and cynomolgus monkeys. Nasopharyngeal mucus was collected at frequent intervals during periodic nasal instillations of BaP (and for dogs 24 h after instillation) for analysis of BaP and its metabolites. During and up to 48 h after nasal instillation of [14C]BaP, blood, urine and feces were collected to determine BaP clearance from the nose. High pressure liquid chromatographic analysis of organic phase extracts of nasopharyngeal mucus demonstrated that [14C]BaP instilled in either turbinate region was metabolized to dihydrodiols, quinones, phenols and tetrols in both species. Phenols were the major metabolic product, although all treated animals produced trans-7,8-dihydrobenzo[a]pyrene-7,8-diol. The dog mucus sampled at 24 h had no detectable radioactivity. The excreta from both species contained only small amounts of the instilled radioactivity. There was no distinctive pattern of metabolite production based on instillation site.

Administration, Intranasal↗
PubMed1989

Effect of food restriction on benzo(a)pyrene binding to DNA in Wistar rats.

A study was carried out to assess the binding of the carcinogen benzo[a]pyrene to DNA in different tissues under in vivo and in vitro conditions in Wistar rats which have been subjected to different levels of food restriction. The results showed that there was a significant increase in the binding of benzo[a]pyrene to hepatic DNA in food restricted animals in in vivo experimentation although this was not observed under in vitro conditions. There was a decrease in binding to pulmonary DNA and no change for renal DNA.

Animals↗
PubMed1995

Inhibition of DNA synthesis in primary cultures of adult rat hepatocytes by benzo[a]pyrene and related aromatic hydrocarbons: role of Ah receptor-dependent events.

Studies were conducted to examine the effects of benzo[a]pyrene (BaP) and related-aromatic hydrocarbons (AHs) on the DNA synthetic profiles of adult rat hepatocytes in primary culture. Scheduled DNA synthesis in control cultures peaked at 64 h and was negligible by 72 h after initial seeding of freshly isolated hepatocytes. A concentration-dependent inhibition of DNA synthesis was observed in 1-day old hepatocyte cultures treated with BaP (0.3-30 microM) for up to 28 h. Comparable inhibitory responses were observed in cultures treated for 24 h with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 0.01-1 nM) or 2,3,7,8-tetrachlorodibenzofuran (TCDF, 0.01-1 nM), but not in cultures treated with perylene (0.01-100 nM) or benzo[e])pyrene (1-1000 nM). Ethoxyresorufin-O-deethylase (EROD) activity was highly inducible in hepatocytes challenged for 24 h with BaP (0.3-3 microM) or TCDD (0.1-100 nM) with peak induction observed at 12 or 36 h after chemical challenge, respectively. To determine if DNA synthesis inhibition by these agents involved aryl hydrocarbon receptor (AhR)-related events, subsequent experiments were conducted to examine the interactions of alpha-naphthoflavone (alpha-NF) and ellipticine (ET) with BaP and TCDD in this cell system. Pretreatment with alpha-NF (10 nM) for 24 h prevented the inhibitory effects of both BaP (3 microM) and TCDD (1 nM), while ET (0.01 nM) pretreatment selectively antagonized the effects of BaP (3 microM). Pretreatment of hepatocytes with TCDD or TCDF (1 nM) for 24 h before the onset of DNA synthesis followed by challenge with BaP (3 microM) partially antagonized the inhibitory response to BaP. These data implicate AhR-related signal transduction in the inhibition of hepatocyte DNA synthesis by BaP and related AHs and suggest that in the case of BaP, metabolism by cytochrome P450 to toxic intermediates contributes to the inhibitory response.

Analysis of Variance↗
PubMed1982

Excimer fluorescence of pyrene-tropomyosin adducts.

Studies of the fluorescence of N-(1-pyrene)maleimide and N-(1-pyrenyl)iodoacetamide adducts of rabbit skeletal muscle tropomyosin revealed the presence of excimer fluorescence characterized by a broad emission band at 480 nm with a shoulder at 505 nm. Monomer fluorescence decay exhibited different lifetimes, viz., about 3, 22 and 87 ns for the pyrenemaleimide adduct; about 2.5, 11 and 51 ns for the aminolyzed maleimide adduct; and 2.5, 15 and 74 ns for the pyrenyliodoacetamide adduct. Almost identical excimer fluorescence lifetimes were found for all adducts; about 9, 35, and 65 ns. Excimer fluorescence was sensitive to changes in ionic strength and pH of the medium while monomer fluorescence did not change. The protein denaturants guanidine hydrochloride and urea caused dissociation of the two tropomyosin subunits and partial disappearance of excimer fluorescence, but not as effectively as the hydrophobic surfactant sodium dodecyl sulfate. The sensitivity of excimer fluorescence to changes in the microenvironment make these pyrene derivatives very useful probes for studying conformational changes and binding interaction of tropomyosin with other contractile proteins. The unique location of the excimer probe at tropomyosin Cys-190 and its characteristic long lifetimes could make it useful in time-resolved anisotropy studies and fluorescence energy-transfer experiments.

Animals↗
PubMed1995

Conformational studies of the (+)-trans, (-)-trans, (+)-cis, and (-)-cis adducts of anti-benzo[a]pyrene diolepoxide to N2-dG in duplex oligonucleotides using polyacrylamide gel electrophoresis and low-temperature fluorescence spectroscopy.

Using polyacrylamide gel electrophoresis (PAGE) and low-temperature, laser-induced fluorescence line narrowing (FLN) and non-line narrowing (NLN) spectroscopic methods, the conformational characteristics of stereochemically defined and site-specific adducts derived from the binding of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (anti-BPDE, a metabolite of the environmental carcinogen benzo[a]pyrene), to DNA were studied. The focus of these studies was on the four stereochemically distinct anti-BPDE modified duplexes 5'-d(CCATCGCTACC).(GGTAGCGATGG), where G denotes the lesion site derived from trans or cis addition of the exocyclic amino group of guanine to the C10 position of either (+) or (-)-anti-BPDE. PAGE experiments under non-denaturing conditions showed that the (+)-trans adduct causes a significantly greater retardation in the electrophoretic mobility than the other three adducts, probably the result of important adduct-induced distortions of the duplex structure. Low-temperature fluorescence studies in frozen aqueous buffer matrices showed that the (+)-trans adduct adopts primarily an external conformation with only minor interactions with the helix, but a smaller fraction (approximately 25%) appears to exists in a partially base-stacked conformation. The (-)-trans adduct exists almost exclusively (approximately 97%) in an external conformation. Both cis adducts were found to be intercalated; strong electron-phonon coupling observed in their FLN spectra provided additional evidence for significant pi-pi stacking interactions between the pyrenyl residues and the bases. FLN spectroscopy is shown to be suitable for distinguishing between trans and cis adducts, but lesions with either (+)- or (-)-trans, or (+)- or (-)-cis stereochemical characteristics showed very similar vibrational patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1986

Benz[a]anthracene-induced alterations in the metabolic activation of benzo[a]pyrene by hamster embryo cell cultures.

Co-administration of benz[a]anthracene (BA) with benzo[a]pyrene (B[a]P) to hamster embryo cell cultures for 24 h resulted in a decrease in the metabolism of benzo[a]pyrene by 40%, a decrease in the level of binding of B[a]P to DNA by 70% and a 10-fold reduction in mutation induction in a hamster embryo cell-mediated V79 cell mutation assay. This data indicates that the biological effects of co-administration of BA with B[a]P result from inhibition of the metabolic activation of B[a]P rather than induction of enzymes that detoxify the B[a]P.

Animals↗
PubMed1986

Differences in the covalent binding of benzo[a]pyrene, safrole, 1'-hydroxysafrole, and 4-aminobiphenyl to DNA of pregnant and non-pregnant mice.

The effects of pregnancy on the covalent binding of several carcinogens to DNA were investigated in mice. Non-pregnant or timed-pregnant (18th day of gestation) ICR mice of similar age were treated with benzo[a]pyrene (BP, 200 mumol/kg), safrole (600 mumol/kg), 1'-hydroxysafrole (400 mumol/kg), 4-aminobiphenyl (4-ABP, 800 mumol/kg), or trioctanoin (4 ml/kg) per os. Tissue DNA adduct levels at 24 h after carcinogen treatment were analyzed via a 32P-postlabeling assay. Pregnancy lowered the binding of the ultimate carcinogenic metabolite of BP, 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE I), to liver and lung DNA by 29-41%, but not the binding of other metabolites. The binding of safrole and its proximate carcinogen, 1'-hydroxysafrole, to liver and kidney DNA was increased 2.3-3.5 fold. Pregnancy decreased the binding of 4-ABP to liver DNA by approximately 18% but increased its binding to kidney DNA by 67%. The results suggest that exposure to some genotoxic compounds, especially those requiring conjugation reactions for metabolic activation, may be more hazardous during pregnancy than in the non-pregnant state.

Aminobiphenyl Compounds↗
PubMed1988

Different response of chicken embryo fibroblasts and hepatocytes to the interference of certain antioxidants on the binding of [G-3H]benzo[a]pyrene to DNA.

The effects of treatment with reduced glutathione, cysteine and ascorbic acid on chick embryo fibroblasts and hepatocytes cultured in vitro in the presence of [G-3H]benzo[a]pyrene ([3H]BP) were studied in an attempt to evaluate the capacity of these antioxidants to interfere with the binding of the carcinogen to DNA in these two cell populations. The results revealed that in the absence of treatment with antioxidants, the carcinogen bound to the DNA of the hepatocytes less than it did to that of the fibroblasts, despite the fact that the two cell populations manifest more or less the same uptake of [G-3H]benzo[a]pyrene from the medium. Moreover the hepatocytes, unlike the fibroblasts, seemed to reap little advantage from the known capacity of the antioxidants to interfere with the binding of the carcinogen to DNA.

Animals↗
PubMed1991

Visualization of a protein involved in seric immune complexes of patients with epithelial tumors having elevated levels of anti-'benzo[a]pyrene-like' IgA.

Many authors have previously described that several types of human cancer were associated with elevated levels of IgA and IgA-containing immune complexes. We have recently identified and characterized IgA directed against a "benzo[a]pyrene-like' antigen in sera of patients with mammary tumors. Circulating immune complexes from these sera were precipitated and analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A 18-20-kDa protein was found closely associated with high levels of anti-'benzo[a]pyrene-like' IgA in sera of patients having a proliferative pathology.

Antibodies, Monoclonal↗
PubMed1993

Covalent binding of (+) 7S-trans-7,8-dihydrobenzo [a]pyrene-7,8-diol to trout DNA: P-450- and peroxidation-dependent pathways.

Bioactivation in vivo of pure (+) 7S-trans-7,8-dihydrobenzo[a]pyrene- 7,8-diol ((+) BP-7,8-DHD) was investigated in rainbow trout. Embryos, microinjected with 0.01-1.0 microgram of [3H]-(-)-7S-trans-7,8-dihydrobenzo[a]-pyrene-7,8-diol-anti-9,10-epoxide ((-) anti-BPDE), exhibited a dose-dependent increase in DNA adduction. Subsequently, microinjection of trout embryos with [14C] (+) BP-7,8-DHD also demonstrated a dose-dependent increase in DNA adduction. To determine the relative contribution of P-450-dependent versus peroxidation-dependent epoxygenation of (+)-BP-7,8-DHD, trout embryos were co-injected with [14C]-(+)-BP-7,8-DHD and either beta-naphthoflavone (BNF) (CYP1A1 inducer) or carbon tetrachloride (CCl4) (lipid peroxidation enhancer). Co-injection with BNF tended to enhance covalent binding to DNA, which was consistent with rapid induction of CYP1A1. Co-injection with CCl4, significantly increased covalent binding of [14C]-(+)-BP-7,8-DHD to DNA, suggesting a contribution from non-enzymic cooxidation. 32P-Postlabeling analysis of liver DNA adducts following i.p. injections of (+) BP-7,8-DHD did not detect appreciable amounts of (-) anti-BPDE-dG from juvenile trout fed control diets or diets containing hydrogen peroxide or BNF. On the contrary, BNF pre-feeding markedly enhanced the levels of an adduct which co-chromatographed with authentic (+) syn-BPDE-dG. These results confirm that trout are capable of metabolically activating BP-DHD to the ultimate carcinogen BPDE and that BNF stimulates CYP1A1-dependent epoxygenation, but peroxidation-dependent activation may not contribute significantly to the bioactivation of BP-7,8-DHD in vivo.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1993

Quantitative analysis of the metabolism of 9,10-dihydrobenzo[a]pyrene by induced rat liver microsomes.

The ability of reduced polycyclic aromatic hydrocarbons to be converted to their fully aromatic forms by the microsomal cytochrome P-450 mixed-function oxidases may assist in the explanation of the mutagenic and tumorigenic activities of these agents. The metabolic conversion of 9,10-dihydrobenzo[a]pyrene (9,10-DHB[a]P) to benzo[a]pyrene (B[a]P) and 9- and/or 10-hydroxy-9,10-DHB[a]P (OH-9,10-DHB[a]P) was quantitatively measured. In beta-naphthoflavone-induced rat liver microsomes, 9,10-DHB[a]P was metabolized to B[a]P with a specific activity of 1.51 nmol B[a]P formed/min/mg microsomal protein. The formation of B[a]P was directly related to incubation time and microsomal protein concentration. Similarly, 9,10-DHB[a]P was converted to OH-9,10-DHB[a]P with a specific activity of 4.48 nmol OH-9,10-DHB[a]P formed/min/mg microsomal protein. Its formation was directly related to incubation time and microsomal protein concentration. The possibility of OH-9,10-DHB[a]P as a metabolic intermediate to B[a]P is discussed.

Animals↗
PubMed1987

The effects of organochlorine pesticides as inducers of testosterone and benzo[a]pyrene hydroxylases.

p,p'-DDE, phenobarbital, dieldrin heptachlor, chlordane and toxaphene induced rat liver microsomes exhibited increased formation of the 4,5-dihydrodiol, 3,6-quinone, 9- and 3-hydroxymetabolites of benzo[a]pyrene and the latter three compounds also induced an increase in the rate of formation of the 9,10-dihydrodiol metabolite. Lindane was inactive as an inducer of benzo[a]pyrene hydroxylase. With the exception of lindane, all the organochlorine pesticides and PB induced testosterone 16 alpha- and 16 beta-hydroxylases; in contrast lindane induced testosterone 6 alpha-, 7 alpha- and 6 beta-hydroxylases and PB also induced testosterone 15 beta-hydroxylase and androstenedione formation. Using a battery of monooxygenase enzyme assays it was evident that there were significant differences between PB and several organochlorine pesticides as inducers of rat hepatic cytochrome P-450-dependent monooxygenases.

Aminopyrine N-Demethylase↗
PubMed1982

Hepatic microsomes from freshwater fish--II. Reduction of benzo(a)pyrene metabolism by the fish anesthetics quinaldine sulfate and tricaine.

1. A single in vivo exposure of brook trout (Salvelinus fontinalis) to a 30.0 mg/l solution of quinaldine sulfate or a 112.5 mg/l solution of tricaine for 5 min significantly reduced the in vitro hydroxylation of benzo(a)pyrene. 2. Since quinaldine sulfate and tricaine formed type I and II binding spectra, respectively, with brook trout hepatic cytochrome P-450, these chemicals probably reduced benzo(a)pyrene hydroxylase enzyme activity by altering the form(s) of cytochrome P-450 responsible for this activity. 3. Hepatic microsomal cytochrome P-450 from brook trout treated with tricaine for 5 min and then placed into fresh water for 24 hr had returned to control levels. 4. Caution should be exercised in the use of quinaldine sulfate or tricaine to anesthetize fish prior to analysis of hepatic microsomal mixed function oxidases.

Aminobenzoates↗
PubMed1982

Distribution and retention of benzo(A)pyrene in rats after inhalation.

Tritium levels in tissues of rats were determined after inhalation of tritiated benzo(a)pyrene (3H-BaP; 500 micrograms/l; activity mass median diameter, 1-2 micrometers) for 1 h. Significant amounts of radioactivity were found in the nasal turbinates, trachea, larynx, lungs, tracheobronchial lymph nodes, kidneys, and liver immediately after exposure. Lower concentrations of radioactivity were found in the brain, testes, and spleen. Clearance of radioactivity from the respiratory tract occurred in two phases; a rapid phase where 50% of the radioactivity cleared by approx. 2 h, and a slower phase that continued for about 2 days after exposure. Radioactivity in the brain, testes, and spleen remained at about the same level during the first day after exposure and then decreased slightly during the second day. Benzo(a)pyrene inhaled in this particulate form was rapidly solubilized, translocated to internal organs, and excreted primarily in feces.

Animals↗
PubMed1983

Benzo(a)pyrene and aniline increase sister chromatid exchanges in cultured rat liver fibroblasts without addition of activating enzymes.

The RL4 rat liver epithelial cell line possesses enzymes capable of bioactivating xenobiotics. This cell line was used without the addition of exogenous activating enzymes to study the genotoxicity of benzo(a)pyrene B(a)P and aniline as measured by the sister chromatid exchange technique. Both increased sister-chromatid exchange (SCE) formation in RL4 cells although B(a)P was more effective than aniline. Pyrene, a structural analogue of B(a)P, demonstrated no genotoxicity. These results indicate that the RL4 cell line containing endogenous bioactivation ability may be useful for genotoxicity studies.

Aniline Compounds↗
PubMed1993

Effect of intratracheally administered lindane on aldrin and benzo(a)pyrene contents in lungs of rats.

Pretreatment with lindane resulted in inhibition of benzo(a)pyrene hydroxylase activity in the lungs of rats. The enzyme activity tended to return to normal 5 days after the administration of lindane. Studies with benzo(a)pyrene and aldrin indicated reduced elimination of these compounds from the lungs of lindane-treated animals, suggesting that lindane may alter the clearance of certain substances or compounds from lungs. The delayed clearance of these compounds from lungs may be an indirect effect of lindane related to inhibition of certain metabolizing enzymes.

Aldrin↗